The UK Prospective Diabetes Study (UKPDS) is a prospective randomized study of different therapies that was set up to determine whether improved blood glucose control of non-insulin dependent diabetes will reduce morbidity and mortality. 4.075 patients have been recruited, with mean age 51 years, mean fasting plasma glucose 11.5 mmol/l. The Clinical study will continue to 1994 with 9 years median follow-up. The allocation to "active therapy" with either sulphonylurea or insulin has provided improved blood glucose control compared with allocation to a "diet policy" (median fasting plasma glucose 7.0 and 8.9 mmol/l respectively). Since 1982, patients have had their fundi assessed by quantitation of retinal photographs at diagnosis and at three yearly intervals. At presentation 23% of patients have retinopathy, defined as microaneurysms, and 9% have more severe retinopathy. Since 1987 the retinopathy has been assessed by a modified "191" grading. Over three years there has been an increase of marked retinopathy, defined as grade 31 31 or worse, to 14% by three years, and to 19% by 6 years. Already 148 patients have had photocoagulation, 1159 patients have had cataract excision, and 61 patients have been registered blind. The main analysis will be to determine whether the policy of improved glucose control will reduce the progress of retinopathy assessed by the incidence of blindness, proliferative retinopathy, maculopathy or by deterioration of the "191" grading. The study will examine both primary prevention and secondary prevention. In addition, several clinical and biochemical variables are being quantitated, e.g. blood pressure, smoking, plasma lipids, microalbuminuria. The degree to which these are associated with the progress of retinopathy will also be assessed. In 1987, a factorial design, prospective randomized trial, of different blood pressure therapies was included to determine whether improved blood pressure control will prevent complications of diabetes. 1139 hypertensive patients have been allocated to tight blood pressure control with either a beta-blocker or ACE inhibitor, or to less-tight control. A satisfactory blood pressure difference has been obtained between the two groups (142/83 and 156/89 respectively), and the study will also be able to determine whether improved blood pressure control, beta-blocker or ACE inhibitor therapy will prevent progress of retinopathy. The application is for funds for (i) to take the retinal photographs in the clinical study in the final year of follow-up, (ii) to complete grading of photographs, (iii) to analyze the data relating to ophthalmological aspects for publication.